We seek to advance understanding of the mechanisms that cause adrenal androgen secretion by the fetal adrenal zone prenatally and by the definitive adrenal cortex during adrenarche, and to improve the diagnosis and treatment of disorders that cause excess adrenal androgen or glucocorticoid secretion, such as premature adrenarche, congenital adrenal hyperplasia, adrenal neoplasms, idiopathic hirsutism, polycystic ovary syndrome, and Cushing syndrome. We also seek to clarify the pathophysiology of primary adrenal insufficiency (Addison's disease) and secondary adrenal insufficiency and to improve the treatment of these conditions. Children with congenital adrenal hyperplasia are being enrolled into a study to test the hypothesis that growth can be normalized, and the side effects of supraphysiologic glucocorticoid treatment avoided, by a regimen of antiandrogen, aromatase inhibitor, and reduced hydrocortisone dose. Additionally, the potential to cure the 21-hydroxylase deficiency form of congenital adrenal hyperplasia by gene therapy is being explored in a newly recognized animal model of this disorder. Patients with Cushing syndrome or a pseudo-Cushing state are being studied by several new diagnostic methods to determine the relative diagnostic efficiency of these new methods compared to the old. Oncogene expression in corticotropinomas is also under study in an attempt to elucidate the molecular basis of Cushing disease.